#HutchinsonGilfordProgeriaSyndrome
#SmoothMuscleCell Progerin transgene drives #EndMT #Atherosclerosis🐭
⏫Aortic Endothelial Cell permeability
⏫Lesional EC infiltr▶️ColIV- & TGFβ1-rich plaque😮
Paracrine of progeroid aortic SMC?😆
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
Journal Session @ #AHA25
Circulating Global Health Knowledge: Key Findings from AHA Journals
Featuring Editors from #CircAHA, #CircImaging, and more
Fri 11/7 @ 2-3:15pm
Room 243
Add to your schedule: https://ahajrnls.org/4ouw4Lw
Submitting your #cardiology manuscript to NEJM?
Learn more about seamlessly transferring your manuscript between @nejm.org and #CircAHA
www.ahajournals.org/circ/nejm-circulation-co...
#TCT2025
Submitting your #cardiology manuscript to NEJM?
Learn more about seamlessly transferring your manuscript between @nejm.org and #CircAHA
www.ahajournals.org/circ/nejm-circulation-co...
#TCT2025
Histone Variants
#SmoothMuscleCell
1⃣H2A.Z
⬇️in #Atherosclerosis
⏫SMC contractile gene
#CircAHA 2018
www.ahajournals.org/doi/10.1161/...
#BMCGenom 2025
bmcgenomics.biomedcentral.com/articles/10....
2⃣H3.3B
⬆️in #AorticDissection
⏫SMC synthetic genes
#Genomics 2023
www.sciencedirect.com/science/arti...
#AllograftVasculopathy
TET2 #DNADemethylase #MethylcytosineDioxygenase, an epigenomic defender of #SmoothMuscleCell contractile phenotype
⏬Interferon IFNγ in SMC
Ascorbic acid
⏫TET2 activity
⏬🐭aortic #GraftArteriopathy
#CircAHA 2021 @ahajournals.bsky.social
www.ahajournals.org/doi/10.1161/...
Join the #CircAHA #AHAJournals Editors at #ESCCongress!
Circulation: The Full Spectrum
Sunday, 8/31 @ 17:30 - 18:30
Add it to your program today!: https://ahajrnls.org/47TBD0p
🫀 #Lymphangiogenesis
#BranchedChainAminoAcid Catabolism
#HeartFailure
Prox1+ #LymphaticEndothelialCell BCKDK (kinase ⏬BCAA degradation) KO➡️
⏫Lymphangiogenesis
⏫Diastolic function
🐭HFpEF (L-NAME+HFD 12 wk)
Src-VEGFR3 axis
#CircAHA 2025 @ahajournals.bsky.social
www.ahajournals.org/doi/full/10....
Higher #FattyAcidOxidation (likely +OXPHOS Adipogenesis mTPRC1) in non-failing ♀️Heart/Cardiomyocyte than ♂️heart
Integrative re-analysis of GTEx bulk RNAseq, snRNAseq, metabolomics
#CircAHA 2025 @ahajournals.bsky.social
www.ahajournals.org/doi/10.1161/...
#CRISPR #RNAEditing #HypertrophicCardioMyopathy
AAV9-hpCas13d/gRNA
⏬30% RQ mutant mRNA
Partially rescue cardiac hypercontractility, LV hypertrophy & cardiomyocyte loss in early onset HCM of 2-mo Myh6 p.R872H/p.R404Q🐭
Resolve multiple🧍MYH7 variants
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
Activating #HexosamineBiosynthesisPathway to treat #PeripheralArteryDisease
Glucosamine i.p. ⏫Reperfusion #Angiogenesis but not #Arteriogenesis in🐭#LimbIschemia (BALB/c, eNOS-/- C57BL/6)
Distinct pathways from VEGFA
ATF4 as a signaling mediator
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
Quantify in vivo #EndothelialCell proliferation
#Aorta #InferiorVenaCava
CDH5-DreER::Ki67-CrexER::R26-GFP🐭
In 8-wk🐭, 8% aortic EC are proliferative over 12-wk period
⏬in YAP1 KO or VEGFR2 KO
#Piezo1 maintains aortic EC division orientation
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
CRISPR transcription activation of Titin in Cardiomyocyte to normalize sarcomeric content & contractile deficits of #hiPSC-cardiomyocyte carrying TTN truncated variant + dCas9-VPR
Cell type specificity⬅️gRNA targeting cardiac-specific cis elements
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
Lung #EndothelialCell Plasticity
Arterialization of General capillary EC in #PulmonaryHypertension
👤#iPAH
🐭Tie2-Cre::PHD2 f/f
🐭Sugen5416+Hypoxia
scRNAseq
#SpatialTranscriptomics Visium
A novel Plvap-DreERT2 gCapEC lineage reporter 🐭
Cool😎
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
Vaccine for #HeartFailure😈
Targeting IGFBP7 as a component Cardiac #EndothelialCell Secretome😎
EC-derived IGFBP7 suppresses insulin signaling & OXPHOS in Cardiomyocytes (🐭🫀, #hiPSC-CM)
Relevance to endothelial senescence?🤔
#CircAHA 2024
www.ahajournals.org/doi/10.1161/...
Tumor-like properties of #SmoothMuscleCell progenies in #Atherosclersis🤠
SMC progenies exhibit
1⃣ #DNADamage #CopyNumberVariation
2⃣Activated Cancer-like signals
3⃣Stem-like growth
Clonality; Non-senescence
SMC KRasG12D transgene ⬆️atherogenesis!
#CircAHA 2024
www.ahajournals.org/doi/abs/10.1...
ADAMTS16 as a causal gene for #BiscupidAorticValve
Targeted Exon seq 304 BAV+301 Ctrl➡️p.H357Q
🐭Adamts16 H355Q/+ in both Tie2+ #EndothelialCell & Isl1+ #SecondHeartField, not Wnt1+ #NeuralCrest, contribute to developmental raphe formation
#CircAHA 2023
www.ahajournals.org/doi/abs/10.1...
Carotid Artery or Aortic Valve tissue #ExtracelluarVesicle
Vesiculomics 1942 proteins 1083 microRNAs -> Novel signaling mediators for #Calcification
#SmoothMuscleCell FGFR2
VIC Wnt5A
Crazy loads of data🔥👍
@markcblaser.bsky.social #CircAHA 2023
www.ahajournals.org/doi/full/10....
Selectively targeting IGF2R−HLA-DR+ inflammatory, not IGF2R+HLA-DR− phagocytic, IFNγ-stimulated #Macrophage subpopulation using a PLK1 inhibitor BI-2536 to treat #Atherosclerosis
Multiomics: scRNAsq, 242-CD Flow cytometry, proteomics😎
#CircAHA 2023
www.ahajournals.org/doi/10.1161/...
Also, a critical biomechanical role of Palmdelphin in #EndothelialCells
Palmdelphin regulates nuclear resilience to mechanical stress in the endothelium
Via Nuclear actin cap, RanGAP1-#RanGTPase & #Exportin 1-p53-p21🤠
Lena Claesson-Welsh lab #CircAHA 2021
www.ahajournals.org/doi/10.1161/...
